The PDE4 inhibitor roflumilast improves memory in rodents at non-emetic doses

Behavioural Brain Research
T VanmierloJ Prickaerts

Abstract

Enhancement of central availability of the second messenger cAMP is a promising approach to improve cognitive function. Pharmacological inhibition of phosphodiesterase type 4 (PDE4), a group of cAMP hydrolyzing enzymes in the brain, has been shown to improve cognitive performances in rodents and monkeys. However, inhibition of PDE4 is generally associated with severe emetic side-effects. Roflumilast, an FDA-approved PDE4 inhibitor for treatment of chronic obstructive pulmonary disease (COPD), is yielding only mild emetic side effects. In the present study we investigate the potential of roflumilast as a cognition enhancer and to determine the potential coinciding emetic response in comparison to rolipram, a classic PDE4 inhibitor with pronounced emetic effects. Cognition enhancement was evaluated in mice and it was found that both roflumilast and rolipram enhanced memory in an object location task (0.03mg/kg), whereas only roflumilast was effective in a spatial Y-maze (0.1mg/kg). Emetic potential was measured using competition of PDE4 inhibition for α2-adrenergic receptor antagonism in which recovery from xylazine/ketamine-mediated anesthesia is used as a surrogate marker. While rolipram displayed emetic properties at a dose 10...Continue Reading

References

Nov 1, 1988·Behavioural Brain Research·A Ennaceur, J Delacour
May 1, 1988·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·W Krause, G Kühne
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·C H BaileyE R Kandel
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·M BaradE Kandel
Sep 24, 1999·Pharmacology, Biochemistry, and Behavior·J S SilvestreJ M Palacios
Jan 12, 2002·British Journal of Pharmacology·A RobichaudC C Chan
Dec 4, 2004·The Journal of Clinical Investigation·Bing GongOttavio Arancio
Jun 18, 2005·NeuroImage·Masahiro FujitaRobert B Innis
Dec 22, 2006·Journal of Medicinal Chemistry·Stephen A Hitchcock, Lewis D Pennington
Mar 14, 2007·Archives of Neurology·Craig S McLachlanStacey K H Tay
Dec 20, 2007·Neuroreport·Natalie N BraunS Hossein Fatemi
Aug 19, 2008·Psychopharmacology·Olga A H ReneerkensJos Prickaerts
Mar 6, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Kris RuttenJos Hhj Prickaerts
Aug 14, 2009·Neurobiology of Aging·Tim VanmierloMonique Mulder
Sep 18, 2009·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Qi GuoRoger N Gunn
Oct 12, 2010·Bioorganic & Medicinal Chemistry Letters·Michel GallantYves Girard
Jan 7, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yun-Feng LiHan-Ting Zhang
Jan 13, 2011·Drugs of Today·J L Izquierdo, J Aparicio
Feb 15, 2011·Behavioural Brain Research·Lianne RobinsonGernot Riedel
Jun 9, 2011·British Journal of Pharmacology·O BrunoR Ricciarelli
Apr 12, 2012·Behavioural Brain Research·Sven AkkermanJos Prickaerts
Jun 29, 2012·Neurobiology of Aging·Annerieke S R SierksmaDaniel L A van den Hove
Feb 26, 2013·Neuropathology and Applied Neurobiology·Helen LingT Revesz
Jul 26, 2013·Expert Opinion on Therapeutic Targets·Wito RichterMarco Conti
May 13, 2014·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Eva BollenJos Prickaerts
Jun 27, 2014·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Marco PetersTim Tully
Oct 7, 2014·Expert Opinion on Therapeutic Patents·Ana Martinez, Carmen Gil
Dec 3, 2014·European Journal of Pharmacology·Sobhana George Sugin Lal JabarisChidambaram Saravana Babu
Dec 3, 2014·Neurobiology of Learning and Memory·P R A HeckmanJ Prickaerts
Jul 28, 2015·British Journal of Pharmacology·Roberta Ricciarelli, Ernesto Fedele

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Citations

Apr 4, 2017·Experimental Neurology·Edward W VogelBarclay Morrison
Aug 5, 2017·Expert Opinion on Investigational Drugs·Jos PrickaertsArjan Blokland
Feb 15, 2018·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Akihiro TakanoChrister Halldin
Jun 10, 2020·Behavioural Pharmacology·Ahsas Goyal, Debapriya Garabadu
Aug 14, 2020·International Journal of Molecular Sciences·Graeme B BolgerThomas van Groen
Apr 3, 2019·Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete·Andreas PinterRotraut Mössner
Aug 10, 2019·Frontiers in Immunology·Melissa SchepersTim Vanmierlo
Feb 23, 2019·Frontiers in Molecular Neuroscience·Susan McQuownMarco Peters
Aug 1, 2020·Neuroscience Letters·Lal Jabaris S SuginK Narayan Sunil
Sep 20, 2019·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Seyed Mohammad NabaviMohammad Hosein Farzaei
Dec 6, 2020·Neurobiology of Learning and Memory·Susan McQuownMarco Peters
Dec 20, 2020·The European Journal of Neuroscience·Jéssica M BonatoRúbia Maria Weffort de Oliveira
Feb 12, 2020·Neuroscience and Biobehavioral Reviews·Elentina K ArgyrousiJos Prickaerts
Jul 29, 2020·Current Drug Targets·Vivek K SharmaShareen Singh
Jun 14, 2020·Current Topics in Medicinal Chemistry·Mayasah Y Al-Nema, Anand Gaurav
Jun 3, 2021·International Journal of Molecular Sciences·Weixia ZhongNissar A Darmani
Jan 25, 2018·Journal of Medicinal Chemistry·Yinuo WuHai-Bin Luo
May 8, 2020·Neurobiology of Learning and Memory·Jeferson Machado Batista SohnCristina Aparecida Stern

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